Harnessing Polyhydroxyalkanoates and Pressurized Gyration for Hard and Soft Tissue Engineering

Basnett, Pooja; Edirisinghe, Mohan; Taylor, Caroline S.; Illangakoon, Upulitha Eranka; Dawson, Jonathan I.; Kanczler, Janos M.; Behbehani, Mehrie; Humphrey, Eleanor J.; Majid, Qasim A.; Lukasiewicz, Barbara; Nigmatullin, Rinat; Heseltine, Phoebe; Oreffo, Richard O.C.; Haycock, John W.; Terracciano, Cesare; Harding, Siân E.; Roy, Ipsita

doi:10.1021/acsami.0c19689

Cited by 31 publications

(29 citation statements)

References 76 publications

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“…The polymer PHB shows excellent properties and great potential in bone tissue engineering. PHB-based nanocomposites have been widely described [12]. Among them, PHB is well known and widely investigated in biomedical applications due to its high biodegradability and biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

Polyhydroxybutyrate-Based Nanocomposites for Bone Tissue Engineering

et al. 2021

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Bone-related diseases have been increasing worldwide, and several nanocomposites have been used to treat them. Among several nanocomposites, polyhydroxybutyrate (PHB)-based nanocomposites are widely used in drug delivery and tissue engineering due to their excellent biocompatibility and biodegradability. However, PHB use in bone tissue engineering is limited due to its inadequate physicochemical and mechanical properties. In the present work, we synthesized PHB-based nanocomposites using a nanoblend and nano-clay with modified montmorillonite (MMT) as a filler. MMT was modified using trimethyl stearyl ammonium (TMSA). Nanoblend and nano-clay were fabricated using the solvent-casting technique. Inspection of the composite structure revealed that the basal spacing of the polymeric matrix material was significantly altered depending on the loading percentage of organically modified montmorillonite (OMMT) nano-clay. The PHB/OMMT nanocomposite displayed enhanced thermal stability and upper working temperature upon heating as compared to the pristine polymer. The dispersed (OMMT) nano-clay assisted in the formation of pores on the surface of the polymer. The pore size was proportional to the weight percentage of OMMT. Further morphological analysis of these blends was carried out through FESEM. The obtained nanocomposites exhibited augmented properties over neat PHB and could have an abundance of applications in the industry and medicinal sectors. In particular, improved porosity, non-immunogenic nature, and strong biocompatibility suggest their effective application in bone tissue engineering. Thus, PHB/OMMT nanocomposites are a promising candidate for 3D organ printing, lab-on-a-chip scaffold engineering, and bone tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Polyhydroxybutyrate-Based Nanocomposites for Bone Tissue Engineering

et al. 2021

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“…P(3HB) was produced according to previously established methods [ 43 ] and was isolated using the soxhlet extraction method from the Gram-positive bacteria Bacillus subtilis OK2 strain which was previously provided as a gift from Prof Fujio Kawamura, Department of Life Sciences, Rikkyo University, Japan. All the chemicals used for the growth of Bacillus subtilis OK2 strain, and the polymer extraction, were purchased from Sigma-Aldrich Co (Gillingham, UK) and VWR Chemicals (Poole, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the generation of a tailored delivery system for PAD inhibitors, including Cl-amidine, is warranted. In the current study, an attempt to develop targeted delivery approaches for Cl-amidine took advantage of using the polyhydroxyalkanoate (PHA) biopolymers, which are already used and were previously validated in regenerative studies [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Furthermore, a proposed anti-cancerous effect of Cl-amidine was assessed, upon its co-administration with rapamycin, through investigating its effect on VEGF expression in a mammalian breast cancer cell line (SK-BR-3).…”

Section: Introductionmentioning

confidence: 99%

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres

Ahmed

Puthussery

Basnett

et al. 2021

IJMS

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This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4–5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies.

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“…The ideal bone-substitute material should be biodegradable in order to eliminate the need for a secondary surgery [ 30 , 31 ] and osteoconductive to promote bone regeneration [ 32 , 33 , 34 ]. The three-dimensional (3D) scaffold structure should have pore sizes larger than 100 µm and a highly interconnected pore structure to facilitate bone ingrowth, nutrient transport, and degradation of products in an acid–base balance.…”

Section: Orthopedic Applicationsmentioning

confidence: 99%

Special Features of Polyester-Based Materials for Medical Applications

Darie-Niță¹,

Râpă

Frąckowiak

2022

Polymers

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This article presents current possibilities of using polyester-based materials in hard and soft tissue engineering, wound dressings, surgical implants, vascular reconstructive surgery, ophthalmology, and other medical applications. The review summarizes the recent literature on the key features of processing methods and potential suitable combinations of polyester-based materials with improved physicochemical and biological properties that meet the specific requirements for selected medical fields. The polyester materials used in multiresistant infection prevention, including during the COVID-19 pandemic, as well as aspects covering environmental concerns, current risks and limitations, and potential future directions are also addressed. Depending on the different features of polyester types, as well as their specific medical applications, it can be generally estimated that 25–50% polyesters are used in the medical field, while an increase of at least 20% has been achieved since the COVID-19 pandemic started. The remaining percentage is provided by other types of natural or synthetic polymers; i.e., 25% polyolefins in personal protection equipment (PPE).

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Harnessing Polyhydroxyalkanoates and Pressurized Gyration for Hard and Soft Tissue Engineering

Cited by 31 publications

References 76 publications

Polyhydroxybutyrate-Based Nanocomposites for Bone Tissue Engineering

Polyhydroxybutyrate-Based Nanocomposites for Bone Tissue Engineering

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres

Special Features of Polyester-Based Materials for Medical Applications

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